Ultrasound at very-high-frequency provides non-invasive diagnostic imaging with resolution better than 100 urn. Very-high-frequency ultrasound (VHFU) is of great interest for imaging superficial tissues, such as skin, eye, gastrointestinal mucosa, and arterial plaque. The two main limiting factors for VHFU are the small depth of field and the frequency-dependent attenuation. The small depth of field allows fine-resolution images over only a small axial range about the focus, and the frequency-dependent attenuation limits application of VHFU to shallow imaging. We propose to develop signal-processing and VHFU imaging strategies that will mitigate these two limiting factors. Specifically, we will combine coded-excitation algorithms with annular-array technologies. The specific design of coded signals for VHFU will increase signal-to-noise ratio (SNR), which will permit an increased depth of penetration of VHFU waves. VHFU annular arrays allow dynamic focusing that can significantly increase the depth of field without requiring the large number of elements needed in linear arrays; this greatly simplifies electronics and facilitates implementation for clinical scanning. Coded excitation in ultrasound has never been investigated at very high- frequencies nor has it been combined with state-of-the-art annular arrays. We plan to extend the methodologies to obtain quantitative information about tissue microstructures. This quantitative ultrasound information will lead to a new means of distinguishing diseased from normal tissue and of monitoring disease progression or regression. While the technology and methodology to be developed in this project have general applicability for imaging superficial tissues, this research program will be developed in the context of ophthalmology. The proposed research can lead to significant improvement in evaluation of ophthalmic pathologies such as glaucoma, vitreous membranes, hemorrhage, choroidal tumors, and retinal and choroidal detachment that are challenging to image with conventional high-frequency ultrasound. If successful, the proposed research also will lead to significant improvement of diagnostic ultrasound in other clinical specialties. It will allow obtaining medical images with exquisite resolution, increased depth of field and a greater depth of penetration, and lead to new capabilities for improved diagnostic imaging and disease management. [unreadable] [unreadable] [unreadable]